Sex and Tamoxifen confound murine experimental studies in cardiovascular tissue engineering
Abstract Tissue engineered vascular grafts hold promise for the creation of functional blood vessels from biodegradable scaffolds. Because the precise mechanisms regulating this process are still under investigation, inducible genetic mouse models are an important and widely used research tool. Howe...
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2021-04-01
|
| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-021-87006-3 |
| _version_ | 1819039799409901568 |
|---|---|
| author | Kevin M. Blum Lauren C. Roby Jacob C. Zbinden Yu-Chun Chang Gabriel J. M. Mirhaidari James W. Reinhardt Tai Yi Jenny C. Barker Christopher K. Breuer |
| author_facet | Kevin M. Blum Lauren C. Roby Jacob C. Zbinden Yu-Chun Chang Gabriel J. M. Mirhaidari James W. Reinhardt Tai Yi Jenny C. Barker Christopher K. Breuer |
| author_sort | Kevin M. Blum |
| collection | DOAJ |
| description | Abstract Tissue engineered vascular grafts hold promise for the creation of functional blood vessels from biodegradable scaffolds. Because the precise mechanisms regulating this process are still under investigation, inducible genetic mouse models are an important and widely used research tool. However, here we describe the importance of challenging the baseline assumption that tamoxifen is inert when used as a small molecule inducer in the context of cardiovascular tissue engineering. Employing a standard inferior vena cava vascular interposition graft model in C57BL/6 mice, we discovered differences in the immunologic response between control and tamoxifen-treated animals, including occlusion rate, macrophage infiltration and phenotype, the extent of foreign body giant cell development, and collagen deposition. Further, differences were noted between untreated males and females. Our findings demonstrate that the host-response to materials commonly used in cardiovascular tissue engineering is sex-specific and critically impacted by exposure to tamoxifen, necessitating careful model selection and interpretation of results. |
| first_indexed | 2024-12-21T08:58:57Z |
| format | Article |
| id | doaj.art-e7de3cbd0e39491ab82f2557cb8e8c1f |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-12-21T08:58:57Z |
| publishDate | 2021-04-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-e7de3cbd0e39491ab82f2557cb8e8c1f2022-12-21T19:09:30ZengNature PortfolioScientific Reports2045-23222021-04-0111111310.1038/s41598-021-87006-3Sex and Tamoxifen confound murine experimental studies in cardiovascular tissue engineeringKevin M. Blum0Lauren C. Roby1Jacob C. Zbinden2Yu-Chun Chang3Gabriel J. M. Mirhaidari4James W. Reinhardt5Tai Yi6Jenny C. Barker7Christopher K. Breuer8Center for Regenerative Medicine, The Abigail Wexner Research Institute, Nationwide Children’s HospitalCenter for Regenerative Medicine, The Abigail Wexner Research Institute, Nationwide Children’s HospitalCenter for Regenerative Medicine, The Abigail Wexner Research Institute, Nationwide Children’s HospitalCenter for Regenerative Medicine, The Abigail Wexner Research Institute, Nationwide Children’s HospitalCenter for Regenerative Medicine, The Abigail Wexner Research Institute, Nationwide Children’s HospitalCenter for Regenerative Medicine, The Abigail Wexner Research Institute, Nationwide Children’s HospitalCenter for Regenerative Medicine, The Abigail Wexner Research Institute, Nationwide Children’s HospitalCenter for Regenerative Medicine, The Abigail Wexner Research Institute, Nationwide Children’s HospitalCenter for Regenerative Medicine, The Abigail Wexner Research Institute, Nationwide Children’s HospitalAbstract Tissue engineered vascular grafts hold promise for the creation of functional blood vessels from biodegradable scaffolds. Because the precise mechanisms regulating this process are still under investigation, inducible genetic mouse models are an important and widely used research tool. However, here we describe the importance of challenging the baseline assumption that tamoxifen is inert when used as a small molecule inducer in the context of cardiovascular tissue engineering. Employing a standard inferior vena cava vascular interposition graft model in C57BL/6 mice, we discovered differences in the immunologic response between control and tamoxifen-treated animals, including occlusion rate, macrophage infiltration and phenotype, the extent of foreign body giant cell development, and collagen deposition. Further, differences were noted between untreated males and females. Our findings demonstrate that the host-response to materials commonly used in cardiovascular tissue engineering is sex-specific and critically impacted by exposure to tamoxifen, necessitating careful model selection and interpretation of results.https://doi.org/10.1038/s41598-021-87006-3 |
| spellingShingle | Kevin M. Blum Lauren C. Roby Jacob C. Zbinden Yu-Chun Chang Gabriel J. M. Mirhaidari James W. Reinhardt Tai Yi Jenny C. Barker Christopher K. Breuer Sex and Tamoxifen confound murine experimental studies in cardiovascular tissue engineering Scientific Reports |
| title | Sex and Tamoxifen confound murine experimental studies in cardiovascular tissue engineering |
| title_full | Sex and Tamoxifen confound murine experimental studies in cardiovascular tissue engineering |
| title_fullStr | Sex and Tamoxifen confound murine experimental studies in cardiovascular tissue engineering |
| title_full_unstemmed | Sex and Tamoxifen confound murine experimental studies in cardiovascular tissue engineering |
| title_short | Sex and Tamoxifen confound murine experimental studies in cardiovascular tissue engineering |
| title_sort | sex and tamoxifen confound murine experimental studies in cardiovascular tissue engineering |
| url | https://doi.org/10.1038/s41598-021-87006-3 |
| work_keys_str_mv | AT kevinmblum sexandtamoxifenconfoundmurineexperimentalstudiesincardiovasculartissueengineering AT laurencroby sexandtamoxifenconfoundmurineexperimentalstudiesincardiovasculartissueengineering AT jacobczbinden sexandtamoxifenconfoundmurineexperimentalstudiesincardiovasculartissueengineering AT yuchunchang sexandtamoxifenconfoundmurineexperimentalstudiesincardiovasculartissueengineering AT gabrieljmmirhaidari sexandtamoxifenconfoundmurineexperimentalstudiesincardiovasculartissueengineering AT jameswreinhardt sexandtamoxifenconfoundmurineexperimentalstudiesincardiovasculartissueengineering AT taiyi sexandtamoxifenconfoundmurineexperimentalstudiesincardiovasculartissueengineering AT jennycbarker sexandtamoxifenconfoundmurineexperimentalstudiesincardiovasculartissueengineering AT christopherkbreuer sexandtamoxifenconfoundmurineexperimentalstudiesincardiovasculartissueengineering |